Safety and effectiveness of the anti‐amyloid monoclonal antibody (mAb) drug lecanemab for early Alzheimer's disease: the pharmacovigilance perspective

The development of humanized IgG1 anti-amyloid monoclonal antibodies, such as lecanemab, provides a promising novel treatment pathway with potential disease-modifying effects for patients with early Alzheimer's disease (AD). Lecanemab, which gained marketing approval by the United States Food and Drug Administration (US FDA) in July 2023, has since been approved in multiple countries, including the United Kingdom (UK). The decision by the UK's Medicines and Healthcare products Regulatory Agency (MHRA) to approve lecanemab in August 2024 followed similar regulatory decisions in the US and Japan. However, at the time of approval, the decision contrasted with that of the European Medicine Agency (EMA) in July 2024. Subsequently, the EMA recommended the marketing approval of lecanemab in November 2024 following a re-examination of further data submitted by the Marketing Authorisation Holder. The UK's National Institute for Health and Care Excellence (NICE) has not recommended lecanemab for use in early AD amid concerns, including treatment cost and the translation of efficacy outcomes into clinically meaningful improvement. The risks of serious adverse events (SAEs), including amyloid-related imaging abnormalities (ARIA), have also emerged from clinical trial data with a concern for the potential for rare, life-threatening events. This narrative review discusses the requirement for a robust method of monitoring the safety and effectiveness of lecanemab in the real-world clinical setting considering recent regulatory decisions. Additionally, the need to evaluate proposed risk minimization measures (RMMs) is discussed considering the resource constraints of healthcare systems, such as those faced by the UK's National Health Service (NHS).